DESCRIPTION: Clinical depression is a powerful risk factor for mortality after an acute myocardial infarction (MI), yet little is known about the underlying mechanisms that account for this effect. The primary purpose of this study is to examine one of the most plausible candidate mechanisms, altered autonomic tone. Four hundred eighty post-MI patients with DSM-IV major or minor depression who are enrolled in the Usual Care arm of the NHLBI-sponsored ENRICHD (Enhancing Recovery in Coronary Heart Disease) clinical trial, and 480 non-depressed post-MI patients excluded from ENRICHD, will be recruited for this study during a two year period from four ENRICHD clinical centers. A 24 hour ambulatory ECG will be recorded after hospital discharge to obtain data on heart rate variability, myocardial ischemia, and ventricular arrhythmias. Patients will be followed up at 18 months, and psychosocial and medical endpoints, including mortality, will be ascertained. The primary analysis will determine whether heart rate variability accounts for the significantly higher mortality expected in the depressed compared to the non-depressed group, and whether this effect is largely concentrated in patients with ventricular arrhythmias and left ventricular dysfunction. The second purpose of the study is to identify clinical features or subtypes of depression that may be associated with a particularly high mortality risk and with altered autonomic tone, such as symptom severity, comorbid anxiety, or hostility. This mechanistic study will complement the clinical data to be obtained from the ENRICHD trial, and it would be considerably more costly and difficult to conduct a comparable study independently. Clarification of the underlying mechanism will greatly enhance the credibility of the epidemiological evidence that depression increases mortality in post-MI patients, and permit further refinements in risk stratification so that the patients at highest risk can be identified and treated the most aggressively.